6-148439903-G-A

Position:

• chr6-148439903-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_015278.5(SASH1):​c.286-281G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 152,068 control chromosomes in the GnomAD database, including 2,998 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.19 (2998 hom., cov: 32)
• Consequence: SASH1 NM_015278.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.609

Genes affected

SASH1 (HGNC:19182): (SAM and SH3 domain containing 1) This gene encodes a scaffold protein involved in the TLR4 signaling pathway that may stimulate cytokine production and endothelial cell migration in response to invading pathogens. The encoded protein has also been described as a potential tumor suppressor that may negatively regulate proliferation, apoptosis, and invasion of cancer cells, and reduced expression of this gene has been observed in multiple human cancers. Mutations in this gene may be associated with abnormal skin pigmentation in human patients. [provided by RefSeq, Oct 2016]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 6-148439903-G-A is Benign according to our data. Variant chr6-148439903-G-A is described in ClinVar as [Benign]. Clinvar id is 1223255.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.269 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SASH1	NM_015278.5	c.286-281G>A		intron_variant		ENST00000367467.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SASH1	ENST00000367467.8	c.286-281G>A		intron_variant		1	NM_015278.5	P1
SASH1	ENST00000367469.5	n.204-281G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28175 AN: 151950 Hom.: 2995 Cov.: 32

Gnomad AFR AF: 0.0810

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.162

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.282

Gnomad SAS AF: 0.104

Gnomad FIN AF: 0.215

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.244

Gnomad OTH AF: 0.209

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.185 AC: 28189 AN: 152068 Hom.: 2998 Cov.: 32 AF XY: 0.183 AC XY: 13601 AN XY: 74346

Gnomad4 AFR AF: 0.0810

Gnomad4 AMR AF: 0.162

Gnomad4 ASJ AF: 0.241

Gnomad4 EAS AF: 0.281

Gnomad4 SAS AF: 0.105

Gnomad4 FIN AF: 0.215

Gnomad4 NFE AF: 0.244

Gnomad4 OTH AF: 0.214

Alfa AF: 0.0699 Hom.: 1893

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.1
DANN	Benign	0.34

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10872615; hg19: chr6-148761039;